MTBR-tau243 — microtubule-binding region of tau containing the residue 243 — is a specific blood biomarker of tau tangle pathology in patients with Alzheimer’s disease (AD), new research shows.
“Plasma MTBR-tau243 reflects changes in tau pathology that occur during the clinical symptomatic phase of AD,” said lead researcher Kanta Horie, cvs pharmacy kansas city missour PhD, an Eisai-sponsored visiting researcher in Department of Neurology, Washington University School of Medicine, St. Louis, Missouri.
Plasma MTBR-tau234 can also be used to stage AD tauopathy, determine if cognitive symptoms are likely due to AD pathology, and holds promise to track the effects of tau-targeting therapies, Horie said.
Horie presented the findings at the 16th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
Translatable from CSF to Plasma
In earlier work, Horie and colleagues showed that MTBR-tau243 in cerebrospinal fluid (CSF) is a specific biomarker of tau tangle pathology in AD.
This latest research shows that the CSF MTBR-tau243 findings translate to plasma, making it more accessible for clinical trials and diagnosis.
The researchers measured MTBR-tau243 and p-tau217 in plasma samples from 35 adults from Washington University’s Knight Alzheimer Disease Research Center (Knight ADRC) and 108 from the Swedish BioFINDER-2 study who underwent tau-PET scans.
Roughly half of participants were amyloid positive (57% for Knight ADRC and 47% for BioFINDER-2) and 35% and 44%, respectively, were cognitively impaired.
In both cohorts, plasma MTBR-tau243 was detected only in individuals positive for tau-PET, Horie reported.
In the Knight ADRC cohort, plasma MTBR-tau243 showed a strong correlation with CSF MTBR-tau243 (Spearman’s Rho, 0.83) and tau-PET (Rho, 0.74), “suggesting that plasma MTBR-tau243 is translatable from CSF and predicts tau-PET,” the researchers note in their late-breaking abstract.
In the BioFINDER-2 cohort, plasma MTBR-tau243 was strongly correlated with tau-PET in the entire cohort and in amyloid-positive individuals (Rho, 0.85 and 0.82, respectively), whereas plasma p-tau217 was less correlated with tau-PET (Rho, 0.71 and 0.58, respectively).
Plasma MTBR-tau243 in amyloid-positive adults exhibited a higher correlation with tau-PET in late Braak stages (when there is extensive neocortical involvement, Rho, 0.82) than early Braak stages (Rho, 0.45).
This implies that plasma MTBR-tau243 recapitulates more advanced pathological stages (neocortical spreading phase) compared with early pathological stages (subcortical accumulation phase), the researchers say.
Additionally, plasma MTBR-tau243 was significantly associated with Mini-Mental State Examination scores in amyloid-positive participants, while plasma p-tau217 was not, suggesting the potential clinical applications of plasma MTBR-tau243 in predicting not only neurofibrillary tangles but also cognitive impairment in AD, they note.
Important Work
Commenting on this research for Medscape Medical News, Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said it’s “important to continue development of biomarkers that represent the various hallmarks of Alzheimer’s disease and all other dementia — for earlier and more accurate diagnosis, eligibility for treatment, and for tracking of treatment response.
“Currently, the fluid biomarkers that are most advanced for Alzheimer’s are predictive of the presence of amyloid plaques in the brain when measured in early stages of the disease, including both the amyloid-beta 42/40 ratio markers and the phospho-tau markers. The MTBR markers may be some of the first tau markers that correlate most closely with tau tangle formation,” Edelmayer said.
“Measuring MTBR tau in either CSF or blood could in the future be a part of a panel of markers that are more representative of the various biological hallmarks of Alzheimer’s disease,” she added, “and could be used to support diagnosis and treatment decisions.
“However, there is still more validation and clinical research needed with this marker before it is ready for broad clinical use. At this time, it is starting to provide value in research settings, such as clinical trials,” Edelmayer cautioned.
Horie is an employee of Eisai Co., Ltd and research associate at Washington University School of Medicine and may receive income based on technology licensed by Washington University to C2N Diagnostics. Edelmayer reports no relevant financial relationships.
16th Clinical Trials on Alzheimer’s Disease (CTAD) conference: Abstract LB02. Presented October 24, 2023.
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